Therapeutic PEG-ceramide nanomicelles synergize with salinomycin to target both liver cancer cells and cancer stem cells

Nanomedicine (Lond). 2017 May;12(9):1025-1042. doi: 10.2217/nnm-2016-0408. Epub 2017 Apr 25.

Abstract

Aim: Salinomycin (SAL)-loaded PEG-ceramide nanomicelles (SCM) were prepared to target both liver cancer cells and cancer stem cells.

Materials & methods: The synergistic ratio of SAL/PEG-ceramide was evaluated to prepare SCM, and the antitumor activity of SCM was examined both in vitro and in vivo.

Results: SAL/PEG-ceramide molar ratio of 1:4 was chosen as the synergistic ratio, and SCM showed superior cytotoxic effect and increased apoptosis-inducing activity in both liver cancer cells and cancer stem cells. In vivo, SCM showed the best tumor inhibitory effect with a safety profile.

Conclusion: Thus, PEG-ceramide nanomicelles could serve as an effective and safe therapeutic drug carrier to deliver SAL into liver cancer, opening up the avenue of using PEG-ceramide as therapeutic drug carriers.

Keywords: cancer stem cells; ceramide; liver cancer; nanomicelles; salinomycin; therapeutic drug carriers.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Ceramides / pharmacology*
  • Ceramides / therapeutic use
  • Drug Carriers / pharmacology*
  • Drug Carriers / therapeutic use
  • Drug Synergism
  • Hep G2 Cells
  • Humans
  • Liver / drug effects
  • Liver / pathology
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / pathology
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / pathology
  • Polyethylene Glycols / pharmacology*
  • Polyethylene Glycols / therapeutic use
  • Pyrans / pharmacology*
  • Pyrans / therapeutic use
  • Rats, Sprague-Dawley

Substances

  • Antineoplastic Agents
  • Ceramides
  • Drug Carriers
  • Pyrans
  • Polyethylene Glycols
  • salinomycin